Construction Of Novel Spiroheterocycles Via 1,5-Hydride Transfer/Cyclization Sequence

As everyone knows, extensive efforts have been paid to the discovery of valuable and practical approaches for the direct C-H bond functionalization, which represents an efficient procedure for introducing complexity and diversity into functionally important compounds. As a significant family member of direct C-H bond functionalization, hydride transfer/cyclization sequence, which could realize C(sp3)-H bond functionalization, has always been a perennial source of fascination to the chemists. Though a plethora of methods for functionalizing the inactive C(sp3)-H bonds via the tert-amino effect have been established, there remain great efforts to exploit such reactions for the reason that the current approaches were mainly enabled by using aldehydes, ketones or imines as hydride acceptor.In this thesis, a zinc chloride catalyzed tandem 1,5-hydride transfer/cyclization process to form spiroheterocycle terahydroquinoline derivatives are developed. In particular, a diverse array of potentially bioactive spiroheterocylic compounds with novel and complex structures were obtained with high yields and diastereoselectivities from readily available starting materials. The procedures feature not only readily available starting materials and simple reaction conditions, but also eco-friendliness.(1) Pyrazol-5-one derivatives are a class of five-member azaheterocycle compounds and found in a broad range of significantly biological profiles. Initially,2-(pyrrolidin-l-yl) benzaldehyde and 1-Phenyl-3-methyl-2-pyrazolin-5-one were selected as model substrates to screen the optimal reaction conditions, and finally,10 mol% of zinc chloride was chose as the best catalyst using alcohol as solvent. A series of new spiropyrazolone derivatives bearing a variety of functional groups were obtained in good to high yields with good to excellent diastereoselectivities (up to 95%yield,>95:5 dr). Additionally, the spiropyrazolone derivatives could be converted into the corresponding novel spriopyrazoline derivatives.(2) Isoxazol-5-one derivatives, which are an important category of five-member heterocycle compounds, exist in many natural productions, pharmaceutical drugs and pesticides. Due to remarkable pharmacological activities, they attract more and more attentions of researchers. We used 2-(pyrrolidin-1-yl)benzaldehyde and 3-methylisoxazol-5(4H)-one as model substrates for screening of the optimal reaction conditions. The best yield and diastereoselectivity was acquired when the reaction was carried out with 10 mol% as catalyst in ethyl acetate at 80℃. A series of novel spiroisoxazol-5-one terahydroquinoline derivatives were obtained in good to high yields with good to excellent diastereoselectivities (up to 97% yield,>95:5 dr). To demonstrate the practical utility, the reaction was performed on gram scale and the desired product was formed in 86% yield with 94:6 dr. Additionally, the spiroisoxazol-5-one derivatives could be converted into the corresponding novel spiropyrazolone.